As has been shown in our previous investigations on the search for new anticonvulsant agents in a group of N-[(4-arylpiperazin-1-yl)-alkyl] 3-substituted pyrrolidine-2,5-diones, the introduction of aromatic area at the position-3 of the imide ring caused considerable growth of anti-seizure activity. It was especially noticeable in case of molecules with chloro atom attached at position-2 to the phenyl ring. In this series of compounds the most active were N-[4-(3-chloro-phenylpiperazin-1-yl)-methyl]-3-(2-chlorophenyl)-pyrrolidine-2,5-dione which showed ED₅₀ value of 14.18 mg/kg in the MES test [1]. Following these finding, in the present work, we have synthesized two series of analogues, containing the chloro atom at the position-3 of the phenyl ring as well as molecules without substituents at the aromatic fragment (Fig. 1).

Fig. 1.

The initial pharmacological screening was performed within the Antiepileptic Drug Development (ADD) Program in Epilepsy Branch, National Institutes of Health, National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [2]. The results obtained revealed that anticonvulsant activity depended on the presence of chloro atom at position-3 of the phenyl ring as well as the kind of substituents at the 4-arylpiperazine fragment.

References
[1] J. Obniska, A. Zagórska, Il Farmaco 2003, 58, 1227-1234.
[2] H.J. Kupferberg, Epilepsia 1989, 30 (Suppl.), 51-56.

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